2.1: Absorption
Overview of Absorption
Drugs initially enter the body through various routes of administration (e.g. oral ingestion, injection, inhalation, absorption through the skin) and then are absorbed. The absorption process requires drug molecules to cross membranes and move into intracellular and extracellular spaces. Drugs cross membranes by diffusion, channel proteins, or active transport through the lipid bilayer. Some drugs must be transported across a membrane by a special carrier or transport protein (especially large molecule drugs). Drugs enter the body through various routes of administration.
Routes of administration
The rate of absorption varies with the route of administration. For some drugs, the amount absorbed may be a small fraction of the dose administered by a specific route. The amount of drug absorbed into circulation divided by the total amount of drug administered equals the bioavailability for that drug by that route. Since intravenous drugs are administered directly into circulation the bioavailability of any drug given intravenously equals 1.0 or 100%. Common routes of administration and characteristics are listed in Table 2.1.
Route |
Typical F (%) |
Comment |
|---|---|---|
|
IV (intravascular) |
100 |
Immediate absorption |
|
IM (intramuscular) |
75 <100 |
Absorption is delayed compared with IV, dependent on the site of administration. A larger volume of drug can be given than with subcutaneous administration. |
|
SC (subcutaneous) |
75 <100 |
Absorption is delayed compared with IV; a smaller volume of drug can be given than through intramuscular administration. Bioavailability depends on the site of administration, vascularity, and the person's hydration status. |
|
SL (sublingual) or buccal (not swallowed) |
varies (35% for nitroglycerin 5 mg) |
Note that although this administration occurs in the person’s mouth, the drug is directly absorbed into systemic circulation, bypassing the hepatic first-pass effect. |
|
PO (oral) |
5 <100 |
Absorption may be slow and influenced by first-pass effect, gastric pH, concomitant medications, and co-morbidities
|
|
rectal |
30 <100 |
Less first-pass; good for drugs with unpleasant taste or in persons who may not be able to take medications by mouth |
|
inhaled |
5 <100 |
Rapid absorption; a good route to deliver anesthetics or drugs intended for the respiratory system |
|
topical |
varies | Local effect |
|
transdermal |
80 <100 |
Slow, no first-pass effect; slow absorption, long duration; the systemic effect may be affected by site of administration or the individual's specific factors (body temperature) |
As an orally or enterally administered drug moves through the gastrointestinal (GI) tract, it may be deactivated by enzymes present in the stomach and duodenum. When a drug enters circulation from the intestines, liver enzymes may break down part of it, and some of the drug molecules may escape to the general circulation. When a significant amount of drug is metabolized in the intestinal wall, portal circulation, or liver before it reaches circulation, the phenomenon is known as first-pass effect or metabolism.
Recall Figure 1.1 , which shows the path a free drug can take as it travels through circulation. Some drugs become protein-bound, rendering the drug inactive, whereas other drugs remain free and bind to a receptor site. The effects of drug-receptor binding are further described in Chapter 3 . Note that several doses of an oral drug may be required before enough free drug stays active in the circulation (therapeutic level) to exert the desired effect or clinical response.
Drugs that undergo high first-pass metabolism have a less predictable therapeutic level. The therapeutic level, as defined above, is independent of the route of administration or first-pass effect. Importantly, a drug with a high first-pass effect given orally results in lower concentrations of the active drug than if the same amount was administered parenterally. To avoid the first-pass effect, some drugs may be administered using alternate routes such as dermal, nasal, inhalation, injection, or intravenous. Alternative routes of administration bypass the liver by entering circulation directly or via absorption through the skin or lungs. Notable drugs with a high first-pass effect include buprenorphine, ethanol, morphine, and tetrahydrocannabinol (THC). Nitroglycerin (NTG) and estrogen are well known to undergo first-pass metabolism and are commonly prescribed as sublingual and transdermal.
Alternative routes of medication have other patient-related problems to consider. For example, injections may be painful or difficult to administer daily, and breaks in the skin create a risk for infection. Injectable drugs can be costly and may cause localized side effects or contribute to fluctuating drug blood levels.
A transdermal route has the primary benefit of slow, steady drug delivery directly into circulation without first passing through the liver. Drugs delivered transdermally enter circulation via a meshwork of small arteries, veins, and capillaries in the skin. This makes the transdermal route particularly useful in clinical situations where the goal is to administer the drug over a long period to control symptoms. For example, a transdermal fentanyl “patch” is used to treat chronic pain, and a nitroglycerin patch is prescribed to treat chronic chest pain. Despite their advantages, skin patches have a significant drawback in that only very small drug molecules can enter the body through the skin, making this route not viable for all types of medications. Additionally, transdermal patches may come dislodged from the patient's skin, and the rate of drug dispersal may be affected by changes in body temperature or externally applied heat.
Inhaling drugs through the nose or mouth is another alternative route for rapid medication delivery that bypasses the liver. The inhalation route may also be particularly effective for medications whose site of action is in the lungs. Metered-dose inhalers have been a mainstay of asthma therapy for decades. Recently, the FDA approved the first over-the-counter prescription naloxone 4 mg nasal spray for substance abuse disorder. Inhalation is an efficient route to reverse the effects of an opioid overdose; naloxone is the standard treatment for opioid overdose.
Other Variables that Affect Absorption
In addition to the route of administration, other variables influence the rate and extent of drug absorption, including the size of the drug molecule, lipid solubility of the drug, the degree of ionization of the drug within the gastrointestinal tract, the pH of the internal environment, gastric emptying rate/motility, GI blood flow, and the presence of other drugs or food within the GI tract.
Size of the Drug Molecule
Drugs vary in size and molecular weight. Drugs with a large molecular weight (MW greater than 1000) are poorly absorbed. Large molecular weight drugs (for example, heparin) are often administered by parenteral or intravenous routes to increase absorption.
Lipid Solubility Drug
The lipid solubility of a drug determines how easily the drug will pass through a membrane. Lipid-soluble drugs pass through membranes readily (including the blood-brain barrier) and are absorbed more quickly than water-soluble drugs. Lipid-soluble drugs often undergo first-pass metabolism. These drugs tend to accumulate in fatty tissues and may be difficult to excrete. Water-soluble drugs tend to stay within circulation.
Ionization of Drugs
Drugs are either weak acids or weak bases and may be ionized (charged) or not ionized. The pH of the environment determines the number of drug molecules that are ionized or not ionized. Ionized drugs are more polar and water-soluble.
pH
The pH of the gut changes from an acidic environment in the stomach to an alkaline environment in the duodenum. Drugs can influence the pH of the gastric environment. For example, an antacid changes the gastric environment to be more alkaline and can influence the absorption of other drugs. A weak acid is more lipid soluble in an acidic environment, and a weak base is more lipid soluble in an alkaline environment. When a drug is more lipid soluble, it can move readily through membranes.
Gastric motility
The rate and extent of absorption following an oral drug administration is highly variable. As noted, gastric pH can influence absorption and how quickly the drug moves through the gut. Most orally administered drugs are primarily absorbed in the small intestine.
Blood flow
Blood flow influences how well a cutaneous or intramuscular injection is absorbed. In hypoperfusion or shock states where blood flow is compromised, drugs may not be well absorbed, and the intravenous route is the best option. Drugs are absorbed more rapidly in areas where blood flow is high.
Presence of other drugs or food in the GI tract
As mentioned previously, other drugs a person is taking can change the pH, gastric motility, and pre-systemic metabolism of a medication. Some drug absorption may vary depending on the person's fasting or fed state (the body digests and absorbs nutrients, and insulin levels are high).
This chapter titled 2.1 Absorption is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by Karen Vuckovic from Introduction to Pharmacology by Carl Rosow, David Standaert, & Gary Strichartz ( MIT OpenCourseWare ) via source content that was edited to the style and standards of the LibreTexts platform; a detailed edit history is available upon request. Figures by Riley Cutler.